Device for directly delivering an active substance within a cell tissue, means for implanting said device and appliances for injecting active substance into said device

ABSTRACT

The invention concerns a device for directly delivering an active substance within all or part of a human or animal tissue cell, characterised in that it is in the form of a hollow tube ( 1 ), whereof the walls in contact with said tissue are provided with perforations ( 5 ) and whereof the distal end ( 2 ) is sealed, while the proximal end ( 3 ) is shaped so as to receive removable closing means, said tube being capable of bearing a pressure of at least 50 bars.

[0001] The invention relates to a device intended to deliver an activesubstance directly within all or some of a human or animal cell tissue.It also relates to the means of implanting this device within thetissue, and to the appliances intended for injecting active substanceinto said device.

[0002] In the remainder of the description and in the claims, theexpression “active substance” will be used to denote any chemically orphysically active substance and, more broadly speaking, any substancecapable of being introduced into the organism whether for diagnostic,therapeutic or even cosmetic purposes.

[0003] Likewise, the expression “human or animal cell tissue” will beused to denote any organ or part of an organ.

[0004] In the context of cancer treatments using ionizing radiation,there are a number of solutions which have been proposed with a view toconcentrating the active principle in the cells of the patient that areto be treated while limiting the destruction of healthy cells.

[0005] Document WO 97/18011 has thus proposed an installation forconcentrating an active principle associated with magnetic vectors inthe cells of a patient that are to be treated. The installation employedis capable of creating a focused magnetic field gradient and then, byincreasing the strength of the magnetic field, of causing the magneticvectors to switch from the non-magnetized state to the magnetized stateso as to cause a lasting aggregation thereof in the area of the cellsthat are to be treated.

[0006] However, even though this installation makes it possible tolimit, or even to eliminate, the irradiation of healthy cells, it isnonetheless cumbersome to implement.

[0007] Also proposed, in document JPS Volume 71, number 4, April '82(page 382) a method which consists in injecting, by an arterial route,an active principle associated with magnetic vectors subjected to anexternal magnetic field, which is then focused on the cells that are tobe treated. However, it is found that a significant proportion of themagnetic vectors aggregate and remain trapped in the vessels of thecirculatory system, thus irradiating a great many healthy cells.

[0008] Still in the context of cancer therapy, cancer cells areadvantageously treated with heat, in addition to the conventional activeprinciples, inasmuch as heat has an immediate cytolytic effect on saidcells. In practice, the cancerous cells are heated up using a microwavetreatment. This therapy thus makes it possible to raise the temperaturein a localized way and thus give rise to hyperthermia.

[0009] Heat treatment is also employed for stopping hemorrhaging,particularly hemorrhaging likely to arise during surgical operations,and thus cause hemostasis. In practice, hemostasis is obtained byelectro-coagulation by means of an electric lancet.

[0010] The problem of concentrating the active principle in the cellsthat are to be treated is not restricted to cancer treatments, but alsorelates to a good many other therapies whether these be chemotherapies,antibiotic therapies, etc.

[0011] Document U.S. Pat. No. 5,569,197 proposes concentrating an activeprinciple via an endolumenal route at atheroma plaques formed on theinternal walls of the arteries. The device employed corresponds to atube made of a material said to be “superelastic” with outside diametergreater than 250 micrometers, advantageously 360 micrometers, and ofwhich the walls at the distal end of said tube have perforations.Furthermore, the distal end of the tube is open and can be equipped witha filament which itself has an opening intended to deliver the activeprinciple. The supple filament has the function of guiding the tube inthe small vessels. The active principle, being in liquid form, isdelivered exclusively to the atheroma plaques by infusion at a pressurenot exceeding 4 atmospheres, that is to say slightly higher than 4 bar.

[0012] First of all, the device described in that document makes itpossible to obtain a therapeutic effect only in vascularized organs,insofar as the device proposed is used exclusively by an endolumenalroute. In addition, the active-principle concentration in the area to betreated is raised only temporarily, the remainder of the activeprinciple diffusing through the organism.

[0013] In other words, the first problem that the invention sets out tosolve is that of providing a device capable of delivering an activesubstance to any organ whatsoever.

[0014] A second problem that the invention sets out to solve, is that ofproviding a device capable of allowing a homogenous release of activesubstance in situ exclusively in all or some of the cell tissue that isto be treated, without any diffusion into the organism.

[0015] Another problem that the invention sets out to solve is that ofproviding a device capable of dispensing any type of active principlewhether this be a chemical active principle or a physical activeprinciple, and in any form whatsoever—liquid, solid or even vapor.

[0016] In order to do this, the present invention proposes a devicecapable of delivering an active substance directly within all or some ofa human or animal cell tissue.

[0017] This device is characterized in that it is in the form of ahollow tube, of which the walls in contact with said tissue are equippedwith at least one perforation, and of which the distal end is plugged,while the proximal end is shaped in such a way as to accommodateremovable closure means, said tube being capable of withstanding apressure of at least 50 bar.

[0018] In other words, the idea that the Applicant has had is to deliveran active principle not via an endolumenal route, but directly to thecell tissue by injecting said active principle into a target area at ahigh pressure of at least 50 bar, making it possible to obtain maximumeffect, including into the thickness of the tissue.

[0019] Faced with this problem, the Applicant developed a device capableof withstanding a high pressure allowing the active principle to beinjected directly into the tissues to a depth that varied according tothe pressure used. Furthermore, and given the high pressure, the devicecan have active principles in liquid, solid or even vapor form passingthrough it.

[0020] In practice, the perforated walls of the hollow tube arepositioned at the target organ to be treated, while the remainder of thetube connects to the outside of the organism, the tube thus remaining inposition for the duration of the treatment. In consequence, the tube viaits proximal end receives the active substance that it delivers via itsperforations exclusively to the tissues that are to be treated.

[0021] As will be explained later, the active substance has to be givensufficient energy that it can be propelled through the perforations,then effectively penetrate the tissues that are to be treated.

[0022] At the same time, the tube must retain a certain suppleness tomake it easier to install within the organism and, more particularly, atthe tissues.

[0023] In order to satisfy these requirements, the choice of thediameter and of the thickness of the tube are the result of a compromisebetween said tube being supple, and its being able to withstand pressureand resist stretching.

[0024] When a chemically active substance is to be injected into thetissues, the pressure may reach 3 000 bar or even 10 000 bar if thedesire is to inject a powder.

[0025] In a first embodiment, in order to withstand such a pressurewhile at the same time maintaining a certain suppleness, the outsidediameter of the tube is between 100 and 250 micrometers, while theinside diameter of the tube is between 50 and 150 micrometers.

[0026] For an outside diameter greater than 250 micrometers, it isnecessary to increase the thickness of the tube in order to withstandthe pressure, which means that the flexibility disappears. By contrast,for an inside diameter smaller than 50 micrometers, the loss of energyof the active substance as it travels down the tube is too great, whichmeans that the active substance cannot be propelled into the tissue thatis to be treated.

[0027] Advantageously, the outside diameter of the tube is equal to 200micrometers while the inside diameter of the tube is equal to 100micrometers.

[0028] Likewise the perforations formed on the walls of the tube aresubstantially circular and have a diameter of between 30 and 70micrometers, advantageously 50 micrometers. In practice, theseperforations are made using a laser.

[0029] For a diameter smaller than 30 micrometers, the perforations aretoo small to allow the active substance to pass. On the other hand, fora diameter greater than 70 micrometers, the opening is too great for thetube to have satisfactory strength.

[0030] Furthermore, in order to withstand an internal pressure which mayas high 10 000 bar, the material used to make the tube is chosen fromthe group comprising stainless steel and titanium. Thus, the radius ofcurvature of the tube obtained is of the order of 1 centimeter, thisbeing without permanent deformation.

[0031] However, any material capable of withstanding high pressures ofthe order of 3 to 10 000 bar can be used.

[0032] Incidentally, in the case of the injection of a physically activesubstance, such as water vapor or alternatively hydrogen peroxide vapor,the pressure is at least 50 bar, and in practice is equal to 200 bar.

[0033] In addition, when using hydrogen peroxide by way of activeprinciple, an additional therapeutic effect is achieved by theconversion of hydrogen peroxide, particularly into nascent oxygen.

[0034] Advantageously, use is made of an aqueous solution of hydrogenperoxide, the concentration of which is between 40 and 60% by volume.

[0035] In this case, given the lower pressure, the outside diameter ofthe tube may be higher without, however, the tube losing it suppleness.

[0036] In consequence, and according to a second embodiment, the outsidediameter of the hollow tube is between 300 and 700 micrometers, whilethe inside diameter is between 100 and 300 micrometers.

[0037] For an outside diameter greater than 700 micrometers, it isnecessary to increase the thickness of the tube in order to withstandthe pressure, which means that the flexibility disappears. By contrast,for an outside diameter smaller than 100 micrometers, the loss in energyof the vapor as it travels along the tube is too great, which means thatit cannot be propelled into the organ that is to be treated.

[0038] Furthermore, and according to this embodiment, the perforationsformed on the walls are substantially circular and have a diameter ofbetween 100 and 200 micrometers, advantageously of 150 micrometers.

[0039] For a diameter smaller than 100 micrometers, the perforations aretoo small to allow an effective amount of the vapor to pass. On theother hand, for a diameter greater than 200 micrometers, the opening istoo large to allow the tube to have satisfactory strength.

[0040] In order to withstand a pressure in practice of the order of 200bar, while at the same time maintaining maximum suppleness andresistance to heat, the tube is advantageously made ofpolytetrafluoroethylene (PTFE) or Teflon ®. Of course, any material thatis equivalent in terms of ability to withstand pressure may beenvisioned.

[0041] Although water vapor or hydrogen peroxide vapor can be injectedinto a tube with the above-described properties, they can also beinjected into a tube identical to the one used for injecting a chemicalactive principle, at a lower pressure, of the order of 200 bar. In sucha case, the medic will have just one device that he will be able to usein situ to administer either chemical active principle or physicalactive principle in the form of vapor.

[0042] According to this embodiment, the part of the tube which is notin contact with the tissue that is to be treated is sheathed with aninsulating material which is supple and resistant to heat.

[0043] In order to achieve a homogenous distribution of activeprinciple, the perforations are formed in a spiral around the part ofthe tube that is intended to be in contact with the organ that is to betreated, with a pitch of between 0.1 and 2 centimeters.

[0044] Furthermore, as already stated, the proximal end of the tube hasremovable closure means. In practice, but without implying anylimitation, these means may be in the form of a threaded plug intendedto collaborate with a corresponding tapping made in the proximal end ofthe tube.

[0045] In addition, in order to participate in the connection betweenthe tube and the appliance intended for injecting active substance,which appliance is described hereinafter, said tube has a conical sealfixed near its proximal end.

[0046] As already stated, use of the device of the invention is notrestricted to oncology but also relates to antibiotic therapy. In thiscontext, the tube of the invention finds a particularly advantageousapplication in orthopedics. What happens is that surgical implantationof a prosthesis may give rise to an infection which is often difficultto treat locally. In such an instance, the surgeon may implant anosteosynthesis element such as a prosthesis, a nail, etc, equipped byany known means with the hollow tube of the invention, which will remainin communication with the surroundings external to the organism.

[0047] By way of example, the microtube may be lodged in a spiral-cutgroove made in the surface of the material implanted in the bone. Inthis case, the active principle injected may be an antibiotic, in theevent of bone infection, or a sealant in the event of a prosthesisworking loose.

[0048] The invention therefore also relates to an osteosynthesis elementequipped with the tube of the invention.

[0049] The invention is also aimed at a means of implanting theabove-described device within a target human or animal organ. Thisimplantation may be performed in various ways.

[0050] According to a first method, the tube is implanted byimage-guided puncturing using a needle. In this case, the implantationmeans is therefore in the form of a needle intended to accommodate thetube, said needle having, over all or part of its length, a slot so thatthe tube can be freed and held in position after the needle has beenwithdrawn.

[0051] According to another method, implantation is performedsurgically. In this case, the implantation means is in the form of aneedle fixed to the distal end of the hollow tube, the fixing beingachieved by any known means.

[0052] According to this technique, if there is a desire for said tubeto be implanted around a target organ, for example the liver,perforations are then made on lengths of tube equal to the length of theneedle, these being separated by unperforated lengths, which may beidentified in particular by deposits of gold for needle takeup, theunperforated lengths thus lying outside of the organ that is to betreated.

[0053] According to another method, implantation is performed by anendovascular route, the tube then constituting the catheter.

[0054] The invention also relates to the appliance intended forinjecting active substance into the device.

[0055] However, the configuration of the appliance may vary according tothe pressure at which the active substance is injected.

[0056] Thus, when the active substance is injected at very highpressure, of the order of 3 to 10 000 bar, the appliance ischaracterized in that it has:

[0057] on the one hand, a means of storing the active principle whichcan be connected to the proximal end of the tube;

[0058] and, on the other hand, means capable of allowing the activesubstance to be injected through the tube.

[0059] In practice, the proximal end of the tube outside the organism isconnected directly to the storage means which is subjected to meanswhich will allow the active substance to be injected into the tube at apressure such that it will be propelled through the perforations so thatit reaches the target area that is to be treated.

[0060] According to a first embodiment, the means of storing the activesubstance is in the form of a cylinder, the central axis of which ishollowed out to form a cylindrical reservoir intended to contain theactive substance, and one of the ends of which is intended to beconnected directly to the proximal end of the tube, while the other endis plugged by a sealed plug that can move axially inside the cylindricalreservoir under the effect of the rod of a piston.

[0061] At the same time, and according to another feature of theappliance, the means capable of allowing the active principle to beinjected into the tube are in the form of a mass intended to be thrownagainst the piston, which will act via its rod on the sealed moving plugthus causing active substance to be ejected into the tube.

[0062] In another embodiment, the active substance is stored in adeformable-walled ampoule which is positioned in the abovementionedcylindrical reservoir, the end of the ampoule being connected by anyknown means to the proximal end of the tube. This embodiment thus makesit possible to have doses of active substance available ready for use.

[0063] Incidentally, the mass may be propelled by various means,particularly by means of a pneumatic system or alternatively of anelectromagnetic system.

[0064] Moreover, when the active substance is a physically activesubstance, particularly water vapor or hydrogen peroxide vapor, theappliance is characterized in that it is has:

[0065] a means of heating the active substance,

[0066] a means of conveying the active substance to the heating means,

[0067] a means of transmitting the heated active substance into thetube.

[0068] As already stated, the physically active substance employed is,in practice, in the form of water vapor or hydrogen peroxide vapor.

[0069] In practice, the means of conveying the active substance and themeans of transmitting the heated active substance to the tube of theinvention are in the form of a stainless steel tube wound around analuminum reel.

[0070] In addition, the active substance heating means is in the form ofa resistive electric element wrapped around the reel-tube assembly.

[0071] According to another feature, the reel is equipped with aplatinum probe connected to the electric system thus allowing thetemperature to be regulated.

[0072] In practice, the water or the hydrogen peroxide is injected intothe stainless steel tube at a minimum pressure of 200 bar and emergesvia the same stainless steel tube after having been heated by the reelto a temperature close to 400° C.

[0073] The invention finally relates to a method of administering anactive substance directly within all or some of a human or animal tissueaccording to which:

[0074] first of all, the tissue that is to be treated is located,

[0075] a hollow tube, the walls of which are intended to be in contactwith the tissue that is to be treated are equipped with at least oneperforation, and the distal end of which is plugged is then introducedinto the organism as far as said tissue, the proximal end of said tubeconnecting to the outside of the organism,

[0076] next, the active substance is injected under a pressure of atleast 50 bar into said tube so that it is delivered to the tissues viathe perforations,

[0077] the proximal end of the tube is finally plugged,

[0078] at the end of the treatment, the tube is withdrawn.

[0079] As already stated, the hollow tube can be introduced into theorganism by any known means and particularly using the implantationmeans described hereinabove.

[0080] Likewise, active substance is injected using an appliance of thetype already described or any equivalent means, the appliance beingdetached from the tube after each injection.

[0081] Of course, the same tube can be used, as desired, to inject achemical or physical active substance. In practice, the surgeon may,when implanting the tube, give rise to hemostasis, if need be, byinjecting vapor.

[0082] Furthermore, the active substance may adopt different forms,particularly liquid or alternatively solid, for example in the form ofnanocapsules, nanoparticles or microparticles. It is thus possible toenvisage all types of active substance, whether these be those used inchemotherapy or alternatively in antibiotic therapy, andantiinflammatories and radioactive products for therapeutic use, thesebeing mentioned without any implied limitation.

[0083] In one advantageous embodiment, the active substance may beassociated with magnetic nanoparticles of ferrite of a size between 100and 1 000 nanometers.

[0084] It then follows that when the active substance is being injectedthrough the tube, the energy imparted to the magnetic nanoparticlesmeans that they behave independently of one another, their mutualmagnetic attraction effectively becoming negligible by comparison withtheir kinetic energy. By contrast, after injection, that is to say insitu, the magnetic attraction encourages the nanoparticles to grouptogether again in the form of clumps measuring about 50 micrometers, inthe organ or the area of the organ that is to be treated.

[0085] In the case of a radioactive active principle, said radioactiveactive principle may adopt two different forms:

[0086] it may either consist of radioactive isotopes grafted ontomagnetic particles;

[0087] or it may be included in the magnetic particle and may consist ofradioactive isotopes of the magnetic elements that make up the magneticparticles.

[0088] Advantageously, the radioactive product may be an emitter of α, βand γ radiation for therapeutic purposes, preferably at low energy, soas to obtain the most localized possible irradiation. It may also bebeneficial to combine a γ-emitter of an energy between 100 and 150kiloelectronvolts (keV) or β+ emitter in order that the location of thenanoparticles can be viewed using a γ-camera. This also makes it easierto calculate the radiation dose.

[0089] As already stated, nanoparticles of ferrite may be used by way ofmagnetic particles.

[0090] In such a case, the stable product yielding the radioactiveproduct by irradiation with neutrons or charged particles isincorporated during the manufacture of ferrite nanoparticles, thecomponents of the ferrite yielding, following irradiation, parasiticradioactive products of very short half-life which therefore decay veryquickly. Thus, only the radioactivity of the chosen therapeuticradioactive element remains.

[0091] In another form of embodiment, an active substance can becombined with liquid mercury (Hg) or mercury in an amalgam in the formof nanoparticles. What happens is that at the time of injection, theliquid mercury adopts the micro-droplet form, the kinetic energy ofwhich is high because of its high density. In situ, that is to say inthe organ, the high surface tension of the mercury encourages themicrodroplets to group together into larger beads thus fixing the activesubstance in the organ that is to be treated.

[0092] In addition, mercury has a radioactive isotope (Hg 197) wellsuited to therapy. Thus, the active principle Hg 197 is included in themercury nanoparticles. Furthermore and as already stated, mercuryproduces amalgams with most metals, which therefore makes it possible tofix other metallic radioactive products in the form of traces, themercury remaining liquid.

[0093] The advantages of the invention will become clearly apparent fromthe exemplary embodiment hereinafter in support of the appended figures.

[0094]FIG. 1 is a depiction of the device of the invention.

[0095]FIG. 2 is a depiction of a first implantation means.

[0096]FIG. 3 is a depiction of a second implantation means.

[0097]FIG. 4 is a depiction of an appliance intended to inject theactive principle into the tube when said active principle is injectedunder very high pressure of the order of 3 000 to 10 000 bar.

[0098]FIG. 5 is a depiction of an appliance of the same type as the onein FIG. 4 according to another form of embodiment.

[0099]FIG. 6 is a depiction of FIG. 5 along the axis II.

[0100]FIG. 7 is a depiction in section of an appliance intended forinjecting active principle when said active principle is injected at apressure of the order of 200 bar.

[0101]FIG. 1 depicts the hollow tube that is the subject of theinvention denoted by the general reference 1. The hollow tube has aplugged distal end (2) while the proximal end (3) is shaped in such away as to accommodate a removable closure means, for example a plug. Inpractice, the proximal end of the tube has a tapping (not depicted)intended to collaborate, by screwing, with the screw thread of the plug.

[0102] The diameter varies according to the pressure to which it issubjected. Thus, if the pressure is of the order of 3 000 bar and over,the outside diameter of the tube is 200 micrometers, while its insidediameter is chosen to be equal to 100 micrometers. If the pressure is ofthe order of 200 bar, the outside diameter is 400 micrometers while itsinside diameter is chosen to be equal to 150 micrometers. Of course, thelength of the tube varies according to the distance between the point ofintroduction of the tube into the organism and the organ that is to betreated.

[0103] Furthermore, in order to allow the active principle to be madeavailable homogeneously, the tube has perforations (5) produced using alaser in a spiral on the part of the tube that is intended to be indirect contact with the tissue to be treated, this being with a pitchequal to 0.5 centimeters for example.

[0104] In addition, in order to make the tube easier to connect to theinjection appliances described hereinafter, the tube near its proximalend has a frustoconical seal. It is pierced at its center with anorifice corresponding to the diameter of the tube.

[0105] In order for the tube to maintain its entire suppleness and to beable to withstand the high pressure, it is made of stainless steel ofgrade A304 (international standard).

[0106]FIG. 2 depicts a first means of implanting the tube within anorgan.

[0107] In this embodiment, implantation is achieved by guided puncturingusing a needle (4). The needle is intended to accommodate the tube andover all or part of its length has a slot (4 a) for freeing the tube andholding it in position once the needle has been withdrawn.

[0108] According to another embodiment, the implantation means is in theform of a needle (6) arranged at the distal end (2) of the tube (1) byany known means, particularly by crimping. The tube is thus “sewn” allaround the member (7) that is to be treated. In this case, and in orderto release active substance exclusively in the organ, the perforationsare formed only on both parts (9) which are in contact with the organ,the parts (8) of the tube remaining outside the organ and being plugged,thus preventing active substance from being released in these regions.

[0109]FIG. 4 depicts the first embodiment of an appliance intended forinjecting active substance into the tube (1) under high pressure of theorder of 3 000 bar and over. This appliance is in the general form of acylinder (10). This cylinder is equipped at one of its ends with atapping (11) intended to collaborate with the screw thread (12) of ascrew (13). The appliance of cylindrical shape (10) also has twocompartments:

[0110] a first compartment (14) located near the plug (13) and intendedto accommodate a cylinder (15) constituting the means of storing theactive substance, the central axis of which is hollowed out so as toform a cylindrical reservoir (16) intended to contain the activesubstance proper;

[0111] a hollow cylindrical second compartment (17) forming a chamber inwhich a piston (18) equipped with a rod (19) is moved in terms oftranslation under the action of a mass (20).

[0112] At its end adjacent to the plug (13) the cylinder (15) also has arecess (22) intended to house a washer, particularly an elastomer washer(23). At its opposite end, the cylinder (15) has a plug (24) intended toplug the cylindrical reservoir (16).

[0113] As depicted in that same figure, the plug (13) is pierced rightthrough along its central axis, so as to allow the passage of the tube(1). To simplify fitting of the tube (1) through the plug (13), thelatter longitudinally has a radial slot (25) (see FIG. 6).

[0114] As already stated, the chamber (17) contains a mass (20) intendedto be thrown against the piston (18). The mass (20) is kept stationaryby means of a magnet (27) positioned in the end of the compartment (17).The mass (20) may be propelled in various ways.

[0115] A first way consists in creating a magnetic field using a winding(26).

[0116] The mass may also be propelled by means of a compressed-airsystem (28) as depicted in FIG. 5.

[0117]FIG. 7 depicts an appliance intended for injecting activesubstance under a pressure of the order of 200 bar. As already stated,in this case, the substance injected is a physically active substance,particularly in the form of water vapor or hydrogen peroxide vapor.

[0118] According to this embodiment, the appliance has:

[0119] a means (21) of heating the water or the hydrogen peroxide;

[0120] a means (22) of conveying the water or hydrogen peroxide;

[0121] and a means (23) of transmitting the vaporized water or hydrogenperoxide.

[0122] The means of conveying water or hydrogen peroxide and the meansof transmitting the vaporized water or hydrogen peroxide are in the formof an aluminum reel (24) of a diameter equal to 100 millimeters and of aheight equal to 60 millimeters, wound with a stainless steel tube (25)of an outside diameter of 1.6 millimeters and of an inside diameter of0.3 millimeters, of a length of between 1,500 and 3 000 millimeters. Theend (22) of the tube (25) corresponds to the means of conveying theactive substance and the end (23) corresponds to the means oftransmitting the vapor to the tube of the invention.

[0123] The assembly comprising reel (24) and stainless steel tube (25)has an actual heating means proper in the form of an electric resistiveelement (26) wrapped around it.

[0124] Furthermore, the reel (24) is fitted with a probe (28) connectedto the electrical power supply (27) which regulates the temperature ofthe reel.

[0125] In practice and as already stated, water is injected at apressure of 200 bar into the stainless steel tube, the water then beingheated by means of the reel to a temperature of 400° C., correspondingto a vapor saturation tension of 200 bar, the vapor being reinjectedinto the tube that is the subject of the invention at a pressure of 200bar.

[0126] In practice, the surgeon will first of all delimit the tissue orthe part of the tissue that is to be treated, and therefore itsposition. He thus determines the length of the tube needed to reach saidtissue from the point of introduction of the tube into the organism. Atthe same time, he chooses the appropriate tube, that is to say the onewhich has perforations positioned in such a way that the activesubstance is released exclusively into the tissue or part of the tissuethat is to be treated. He then positions the tube at the organ that isto be treated, either by guided puncturing or surgically using a needle,or alternatively by an endovascular route. The length of the tube ischosen so that only a short length, of the order of about tencentimeters, remains outside the organism. The proximal end of said tubeis then connected to the appliances described hereinabove.

[0127] As far as the first of these two appliances is concerned, thetube is introduced into the radial slot formed in the plug of theappliance. The tube is then connected to the cavity containing theactive substance by screwing the plug in, which leads to close contactbetween the steel washer and the elastomer washer.

[0128] Once the tube has been connected to the storage means, the massis thrown against the piston so that the active substance is injecteddirectly into the tube and delivered exclusively to the organ that is tobe treated.

[0129] As far as the second appliance is concerned, the tube of theinvention is connected directly to the end of the stainless steel tubeby any known means.

[0130] Of course, and as already stated, the tube may remainedpositioned at the organ throughout the duration of the treatment. Inthis case, after each injection of active substance, the tube is sealedagain. At the end of treatment, the tube will be withdrawn.

[0131] The advantages of the invention are clearly apparent from thedescription. The simplicity of the hardware used and the effectivenessof the treatment in sofaras the active substance can be administered insitu exclusively in the area that is to be treated and deeply within itare of particular note.

1. A device for delivering an active substance directly within all orsome of a human or animal cell tissue, characterized in that it is inthe form of a hollow tube (1), equipped with perforations (5) formedover the entire length of the walls intended to be in contact with thetissue, and of which the distal end (2) is plugged, while the proximalend (3) is shaped in such a way as to accommodate removable closuremeans, said tube being capable of withstanding a pressure of at least 50bar.
 2. The device as claimed in claim 1 , characterized in that theoutside diameter of the tube (1) is between 100 and 250 micrometers,while the inside diameter of the tube (1) is between 50 and 150micrometers.
 3. The device as claimed in one of the preceding claims,characterized in that the outside diameter of the tube is equal to 200micrometers while the inside diameter of the tube is equal to 100micrometers.
 4. The device as claimed in one of claims 2 and 3,characterized in that the perforations (5) are substantially circularand have a diameter of between 30 and 70 micrometers, advantageously 50micrometers.
 5. The device as claimed in one of claims 2 to 4 ,characterized in that the material from which the tube is made is chosenfrom the group comprising stainless steel and titanium.
 6. The device asclaimed in claim 1 , characterized in that the outside diameter of thehollow tube is between 300 and 700 micrometers, while the insidediameter is between 100 and 300 micrometers.
 7. The device as claimed inclaim 6 , characterized in that the perforations formed on the walls aresubstantially circular and have a diameter of between 100 and 200micrometers, advantageously of 150 micrometers.
 8. The device as claimedin one of claims 6 and 7, characterized in that the tube is made ofpolytetrafluoroethylene (PTFE).
 9. The device as claimed in one of thepreceding claims, characterized in that the perforations (5) are formedin a spiral around the part of the tube that is intended to be incontact with the organ (7) that is to be treated, with a pitch ofbetween 0.5 and 2 centimeters.
 10. The device as claimed in one of thepreceding claims, characterized in that the removable closure means arein the form of a plug intended to be screwed onto the proximal end ofthe tube.
 11. An osteosynthesis element equipped with the device that isthe subject of one of claims 1 to 10 .
 12. A means of implanting thedevice that is the subject of claims 1 to 10 within human or animaltissue (7), characterized in that it is in the form of a needle (4)intended to accommodate the tube (1), said needle having, over all orpart of its length, a slot (4 a) so that the tube can be freed and heldin position after the needle has been withdrawn.
 13. A means ofimplanting the device that is the subject of claims 1 to 10 within atarget human or animal organ, characterized in that it is in the form ofa needle (6) fixed to the distal end (3) of the hollow tube (1).
 14. Anappliance intended for injecting active substance into the device thatis the subject of one of claims 1 to 10 , characterized in that it has:on the one hand, a means of storing the active principle which can beconnected to the proximal end of the tube; and, on the other hand, meanscapable of allowing the active substance to be injected through the tube(1).
 15. The appliance as claimed in claim 14 , characterized in thatthe means of storing the active substance is in the form of a cylinder(15), the central axis of which is hollowed out to form a cylindricalreservoir (16) intended to contain the active substance, and one of theends of which is intended to be connected directly to the proximal end(3) of the tube, while the other end is plugged by a sealed plug (24)that can move axially inside the cylindrical reservoir (16) under theeffect of the rod (19) of a piston (18).
 16. The appliance as claimed inclaim 15 , characterized in that the cylindrical reservoir can contain adeformable-walled ampoule of active substance, the end of the ampoulebeing connected to the proximal end of the tube.
 17. The appliance asclaimed in claim 14 , characterized in that the means capable ofallowing the active principle to be injected into the tube are in theform of a mass (20) intended to be thrown against the piston (18). 18.The appliance as claimed in claim 17 , characterized in that the mass(20) is propelled by means of a pneumatic system (26).
 19. The applianceas claimed in claim 17 , characterized in that the mass (20) ispropelled by means of an electromagnetic system (28).
 20. An applianceintended for injecting active substance into the device that is thesubject of one of claims 1 to 10 , characterized in that it has: a meansof heating the active substance, a means of conveying the activesubstance to the heating means, a means of transmitting the heatedactive substance into said device.
 21. The appliance as claimed in claim20 , characterized in that the means of conveying the active substanceand the means of transmitting the heated active substance into saiddevice is in the form of a stainless steel tube wound around a reel. 22.The appliance as claimed in claim 21 , wherein the heating means is inthe form of a resistive electric element wrapped around the reel-tubeassembly.